The papain superfamily of cysteine proteases is widely distributed in diverse species including mammals, invertebrates, protozoa, plants and bacteria. A number of mammalian cathepsin enzymes, including cathepsins B, F, H, K, L, O and S, have been ascribed to this superfamily, and inappropriate regulation of their activity has been implicated in a number of metabolic disorders including arthritis, muscular dystrophy, inflammation, glomerulonephritis and tumour invasion. Pathogenic cathepsin like enzymes include the bacterial gingipains, the malarial falcipains I, II, III et seq and cysteine proteases from Pneumocystis carinii, Trypanosoma cruzei and brucei, Crithidia fusiculata, Schistosoma spp.
The inappropriate regulation of cathepsin K has been implicated in a number of disorders including osteoporosis, gingival diseases such as gingivitis and periodontitis, Paget's disease, hypercalcaemia of malignancy and metastatic bone disease. In view of its elevated levels in chondroclasts of osteoarthritic synovium, cathepsin K is implicated in diseases characterised by excessive cartilage or matrix degradation, such as osteoarthritis and rheumatoid arthritis. Metastatic neoplastic cells typically express high levels of proteolytic enzymes that degrade the surrounding matrix. Also, such diseases are associated with high levels of bone turnover. Hence inhibition of cathepsin K may assist in preventing secondary metastases both by attenuating bone remodelling and the invasiveness of cancer cells.
International patent application WO2010/034788 discloses a number of cysteine protease inhibitors including N-[1-6-(ethynyl-3-oxo-hexahydro-furo[3,2-b]pyrrole-4-carbonyl)-3-methyl-butyl]-4-[5-fluoro-2-(4-methyl-piperazin-1-yl)thiazol-4-yl]-benzamide in the form of the free base which is disclosed therein as Example 2. This compound and its free base are referred to herein respectively as “Compound I” and “Compound I free base”.

It is acknowledged on page 3 of WO2010/034788 that cysteine protease inhibitors of that particular series could also exist in the form of a hydrate. In respect of its use as a pharmaceutical agent, Compound I free base suffers from a number of disadvantages relating to its relatively low water solubility and low thermal stability.
There is therefore a need for a form of Compound I which has one or more of the following properties:                (i) high water solubility        (ii) a high degree of crystallinity        (iii) good moisture stability        (iv) good thermal stability.        